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DUSP4 regulates neuronal differentiation and calcium homeostasis by modulating ERK1/2 phosphorylation.

ABSTRACT: Protein tyrosine phosphatases have been recognized as critical components of multiple signaling regulators of fundamental cellular processes, including differentiation, cell death, and migration. In this study, we show that dual specificity phosphatase 4 (DUSP4) is crucial for neuronal differentiation and functions in the neurogenesis of embryonic stem cells (ESCs). The endogenous mRNA and protein expression levels of DUSP4 gradually increased during mouse development from ESCs to postnatal stages. Neurite outgrowth and the expression of neuron-specific markers were markedly reduced by genetic ablation of DUSP4 in differentiated neurons, and these effects were rescued by the reintroduction of DUSP4. In addition, DUSP4 knockdown dramatically enhanced extracellular signal-regulated kinase (ERK) activation during neuronal differentiation. Furthermore, the DUSP4-ERK pathway functioned to balance calcium signaling, not only by regulating Ca(2+)/calmodulin-dependent kinase I phosphorylation, but also by facilitating Cav1.2 expression and plasma membrane localization. These data are the first to suggest a molecular link between the MAPK-ERK cascade and calcium signaling, which provides insight into the mechanism by which DUSP4 modulates neuronal differentiation.

SUBMITTER: Kim SY

PROVIDER: S-EPMC4356191 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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DUSP4 regulates neuronal differentiation and calcium homeostasis by modulating ERK1/2 phosphorylation.

Kim Sun Young SY Han Yong-Mahn YM Oh Mihee M Kim Won-Kon WK Oh Kyoung-Jin KJ Lee Sang Chul SC Bae Kwang-Hee KH Han Baek-Soo BS

Stem cells and development 20141223 6

Protein tyrosine phosphatases have been recognized as critical components of multiple signaling regulators of fundamental cellular processes, including differentiation, cell death, and migration. In this study, we show that dual specificity phosphatase 4 (DUSP4) is crucial for neuronal differentiation and functions in the neurogenesis of embryonic stem cells (ESCs). The endogenous mRNA and protein expression levels of DUSP4 gradually increased during mouse development from ESCs to postnatal stag ...[more]

PMID: 25397900

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DUSP4 regulates neuronal differentiation and calcium homeostasis by modulating ERK1/2 phosphorylation.

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DUSP4 regulates neuronal differentiation and calcium homeostasis by modulating ERK1/2 phosphorylation.

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